Studies of cell surface markers for rabbit lymphoid cell populations have emphasized rabbit T cells with special reference to those involved in retrovirus infection. Previously reported experiments using human, rabbit or mouse cell lines transfected with HUCD4 or RbCD4, and infected with inactivated or non-inactivated HIV-1 indicate that productive HIV-1 infection is necessary to trigger the apoptotic mechanism. The expression of FAS antigen was significantly increased in HIV-1-infected PBMC from HuCD4 transgenic, but not normal rabbits. HTLV-1-transformed human cell lines have been found to be resistant to apoptosis induction via treatment with a monoclonal antibody to Fas antigen (crosslinking) but are extremely sensitive to apoptosis induced by HIV-1 infection. We have been able to confirm the original finding that induction of apoptosis requires productive infection. This finding has been extended to the mechanistic level using human cell lines. The role of molecules that are known to influence the apoptotic process such as BCL-2, Bax, Bad and BCl-x, are being investigated for their effect on apoptosis induced by HIV-1 infection. The HTLV-1 transformed human cell line, found to be resistant to apoptosis induction via crosslinking of FAS antigen, constitutively expresses BCL-2. Since BCL-2 expression has been found to provide protection against apoptotic cell death, the high level of BCL-2 expression in this cell line may be responsible for the resistance of MT2 to apoptosis induction via crosslinking of the Fas antigen. The level of BCL-2 expression in this cell line is not affected by HIV-1 infection, thus infection must induce apoptosis by a mechanism that circumvents the protective effect of BCL-2. We have previously derived HTLV-1-transformed cell lines that differ in their pathogenic potential: one cell line (RH/K34) causes an ATLL-like disease and death in rabbits, whereas the other (RH/K30) induces a latent infection. The lethal cell line (RH/K34) induces thymocyte depletion and virus produced by this cell line causes apoptosis of human and rabbit lymphocytes. The product of the proto-oncogene vav is constitutively tyrosine phosphorylated in the lethal line, RH/K34, but not in RH/K30. This difference in Vav was linked to the virus by studies showing that an HTLV-I molecular clone from RH/K30, but not that from RH/K34, downregulates Vav phosphorylation in a herpesvirus ateles transformed T cell line upon transfection.